Macrolides are multi-membered lactone rings having one or more deoxy sugars as substituents. Erythromycin, azithromycin, and clarithromycin are macrolides that have bacteriostatic and/or bactericidal activity.
Tacrolimus (FK 506) is also a macrolide antibiotic that is also an immunosuppressive agent. More potent than cyclosporin, tacrolimus reportedly has a selective inhibitory effect on T-lymphocytes.
Pimecrolimus is a macrolactam and a ascomycin derivative that reportedly inhibits production of pro-inflammatory cytokines by T cells and mast cells. The Merck Index 1331 (Maryadele J. O'Neil et al. eds., 13th ed. 2001). Pimecrolimus is reportedly used as an immunosuppressant. Id.
Sirolimus, another macrolide, is reported to be an immunosuppressant. Sirolimus has been administered with cyclosporin and corticosteroids after transplantation to avoid graft rejection. Martindale: The Complete Drug Reference 568 (Sean C. Sweetman ed., Pharmaceutical Press 33rd ed. 2002).
Everolimus, a derivative of sirolimus, is reported to be an immunosuppressant used in organ transplantation. Martindale at 539.
The macrolides are typically obtained by fermentation, although synthetic routes to some are known. Macrolides, as obtained, typically contain several impurities that can be detected by various means, for example high-pressure liquid chromatography (HPLC). Presence of impurities in a pharmaceutical compound is undesirable, and health authorities in many jurisdictions (e.g. the Food and Drug Administration in the United States) have established guidelines relating to acceptable levels of impurities in pharmaceuticals. The need for and commercial utility of methods of reducing the level of impurities in any pharmaceutical are self-evident.